Computational methods for NMR and MS for structure elucidation III: More advanced approaches

Abstract The structural assignment of natural products, even with the very sophisticated one-dimensional and two-dimensional (1D and 2D) spectroscopic methods available today, is still a tedious and time-consuming task. Mass spectrometry (MS) is generally used for molecular mass determination, molecular formula generation and MS/MS n fragmentation patterns of molecules. In the meantime, nuclear magnetic resonance (NMR) spectroscopy provides spectra (e. g. 1 H, 13 C and correlation spectra) whose interpretation allows the structure determination of known or unknown compounds. With the advance of high throughput studies, like metabolomics, the fast and automated identification or annotation of natural products became highly demanded. Some growing tools to meet this demand apply computational methods for structure elucidation. These methods act on characteristic parameters in the structural determination of small molecules. We have numbered and herein present existing and reputed computational methods for peak picking analysis, resonance assignment, nuclear Overhauser effect (NOE) assignment, combinatorial fragmentation and structure calculation and prediction. Fully automated programs in structure determination are also mentioned, together with their integrated algorithms used to elucidate the structure of a metabolite. The use of these automated tools has helped to significantly reduce errors introduced by manual processing and, hence, accelerated the structure identification or annotation of compounds.